BCH 4053 Biochemistry I
Fall 2001
Dr. Michael Blaber


Lecture 33

Nutrition


The use of food by organisms is termed nutrition. There are three general categories of food:

Protein

Animals are unable to synthesize certain amino acids (humans can only make 10 of the 20 common amino acids). The amino acids that an animal is unable to synthesize must be obtained from the diet (i.e. by consuming plants or microorganisms), and these amino acids are termed "essential amino acids".

Excess dietary protein becomes a source of metabolic energy

Protein is an important source of nitrogen in the diet. Protein within the body is constantly turning over (i.e. being degraded and resynthesized). Furthermore, there is a general demand for protein synthesis when an organism is growing. The Nitrogen Balance refers to the relationship between the supply and demand for nitrogen (i.e. protein) within an organism.

 

Carbohydrate

Carbohydrates are also an essential structural component of nucleic acids, nucleotides, glycoproteins and glycolipids. However, the principle role of carbohydrate in the diet is production of metabolic energy.

 

Lipid

Fatty acids and triacylglycerols can be used as fuel by many tissues in the human body. Phospholipids are essential components of all biological membranes

 

Fiber

"Dietary fiber" refers to molecules that cannot be broken down by enzymes in the human body.

 

Vitamins and minerals

Vitamins are essential nutrients that are required in the diet because they cannot be synthesized by human metabolic enzymes. Often, only trace levels are required, but a shortage can result in disease or death.

Coenzymes are low molecular weight molecules that provide unique chemical functionalities for certain enzyme/coenzyme complexes.

 

Summary of water soluble and fat soluble vitamins:

Common name

Chemical name

Related cofactor(s)

Water Soluble Vitamins

Vitamin B1

Thiamine

Thiamine pyrophosphate

Vitamin B2

Riboflavin

Flavin adenine dinucleotide (FAD)
Flavin mononucleotide (FMN)

Vitamin B6

Pyridoxal, pyridoxine, pyridoxamine

Pyridoxal phosphate

Vitamin B12

Cobalamin

5'-deoxyadenosylcobalamin
Methylcobalamin

Niacin

Nicotinic acid

Nicotinamide adenine dinucleotide (NAD+)
Nicotinamide adenine dinucleotide phosphate (NADP+)

Vitamin B3

 Pantothenic acid

Coenzyme A

Biotin

 

Biotin-lysine conjugates (biocytin)

Lipoic acid

 

Lipoyl-lysine conjugates (lipoamide)

Folic acid

 

Tetrahydrofolate

Vitamin C

L-ascorbate

 

Fat Soluble Vitamins

Vitamin A

Retinol

 

Vitamin D2

Ergocalciferol

 

Vitamin D3

Cholecalciferol

 

Vitamin E

a-Tocopherol

 

Vitamin K

 

 

 

Vitamin B1: Thiamine and thiamine pyrophosphate

Thiamine is the precursor of thiamine pyrophosphate (TPP):

Niacin (Nicotinic Acid) and nicotinamide coenzymes

Nicotinamide is an essential part of two important coenzymes: nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+).

 

Vitamin B2: Riboflavin

Riboflavin is a constituent of riboflavin 5'-phosphate (flavin mononucleotide, or FMN) and flavin adenine dinucleotide (FAD). The nucleotide part of the molecule does not enter into any chemistry, but is important for recognition and binding to enzymes that will use FMN or FAD as a cofactor.

The isoalloxazine ring is the core structure of the different flavin molecules. It is yellow in color and the word "flavin" is derived from the latin word for yellow, flavus.

 

Vitamin B3: pantothenic acid and coenzyme A

Pantothenic acid is a component of coenzyme A (CoA). The two main functions of CoA are:

  1. Activation of acyl groups (R-COX) for transfer to nucleophilic acceptors
  2. Activation of the a-hydrogen of the acyl group for removal as a proton

Both of these functions involve the reactive sulfhydryl group through the formation of thioester linkages with acyl groups

Vitamin B6: Pyridoxine and pyridoxal phosphate

The biologically active form of vitamin B6 is pyridoxal-5-phosphate (PLP), however, the nutritional requirements can be met by either pyridoxine, pyridoxal or pyridoxol.

PLP participates in a wide variety of reactions involving amino acids, including:

These involve bonds to the amino acid Ca as well as side chain carbons. The wide variety of reactions is due to the ability of PLP to form stable Schiff base adducts with a-amino groups of amino acids:

 

Vitamin B12: Cyanocobalamin

Vitamin B12 is not made by any animal or plant, it is produced by only a few species of bacteria. Once in the food chain, vitamin B12 is obtained by animals by eating other animals, but plants are sadly deficient. Therefore, herbivorous animals (and vegetarians) can suffer a deficiency. The structure contains a cobalt ion, coordinated within a corrin ring structure:

Vitamin B12 (cyanocobalamin) is converted in the body into two coenzymes:

  1. 5'-deoxyadenosylcobalamin (the predominant form)
  2. Methylcobalamin

Vitamin B12 coenzymes participate in three types of reactions:

  1. Intramolecular rearrangements
  2. Reductions of ribonucleotides to deoxyribonucleotides in certain bacteria
  3. Methyl group transfers (these use methylcobalamin for this purpose)

 

Vitamin C (L-Ascorbate)

L-Ascorbate is a reducing sugar (has a reactive ene-diol structure) that is involved in the following biochemical processes:

Almost all animals can synthesize vitamin C (its in the pathway of carbohydrate synthesis). Humans and great apes have suffered a mutation in the last enzyme in the pathway of synthesis for L-ascorbate (mutation occurred about 10-40 million years ago). Since that time, all great apes (of which humans are a member) must get L-ascorbate from their diet (fresh fruits and vegetable contain an abundance). Thus, for the great apes L-ascorbate is a "vitamin" (another way of looking at it is that all great apes suffer an in-born error in metabolism). Humans still have the gene for the enzyme to make vitamin C. However, it has suffered a couple of deletions that introduce a frame shift mutation, in addition to numerous point mutations.

 

Biotin

Biotin acts as a mobile carboxyl group carrier in a variety of enzymatic carboxylation reactions.

Lipoic Acid

Lipoic acid contains two sulfur atoms that can exist as a disulfide bonded pair, or as two free sulfhydrils. Conversion between the two forms involves a redox reaction (the two free sulfhydrils represent the reduced form). Lipoic acid is typically found covalently attached to a lysine side chain in enzymes that use it as a cofactor, as a lipoamide complex.

Folic Acid

Folic acid derivatives (i.e. "folates") are acceptors and donors of one-carbon units for all oxidation levels of carbon (except for the most oxidized form - CO2. See biotin above).

Vitamin A: Retinol

Vitamin A occurs as an ester (Retinyl ester), aldehyde (Retinal) or acidic form (Retinoic acid).

Vitamin D: Ergocalciferol (D2) and cholecalciferol (D3)

Cholecalciferol is produced in the skin of animals by the action of U.V. light on the precursor molecule 7-dehydrocholesterol.

 

Vitamin E: Tocopherol

a-Tocopherol is a potent antioxidant, however, molecular details of its function are not clearly understood.

Vitamin K: Napthoquinone

Vitamin K is essential to the blood-clotting process. Vitamin K is required for the post-translational modification to produce g-carboxy glutamic acid from glutamic acid. Such modified residues can bind Ca2+, which is an essential part of the process in the clotting cascade.


© 2001 Dr. Michael Blaber